Alfa-lipoic acid (also known as thioctic acid or 6,8-dithiooctanoic acid), a coenzyme occurring in mitochondria, has anti-oxidative activity and draws attention as a therapeutic agent for a variety of pathologic conditions induced by oxidative stress, such as arteriosclerosis and cataract. Its reduced state compound, dimercaptooctanoic acid, acts to restore reduced forms of glutathione or vitamin C back from their oxidized forms.
A class of α-lipoic acid derivatives, α-lipoylamino acids, in which α-lipoic acid is bound to glycine, methionine, glutamic acid, valine or the like, respectively are known (Japanese Patent Publication No. S42-1286, and its corresponding U.S. Pat. No. 3,238,224). Japanese Patent Application Publication No. 2000-169371 discloses a salt of α-lipoylaminoethylsulfonic acid with imidazole and its use as an enhancer of glutathione reductase activity.
Upon the above background, the present inventors succeeded in efficient synthesis of metal chelate compounds and their pharmacologically acceptable salts of reduced forms (dihydro-forms) of novel α-lipoylamino acids, found that these compounds possess a tyrosinase inhibiting activity, a melanin production suppressing activity and an elastase inhibiting activity, and completed the present invention through further studies.